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Literature summary for 1.4.3.4 extracted from

  • Herraiz, T.; Aran, V.J.; Guillen, H.
    Nitroindazole compounds inhibit the oxidative activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin to neurotoxic pyridinium cations by human monoamine oxidase (MAO) (2009), Free Radic. Res., 43, 975-984.
    View publication on PubMed

Inhibitors

Inhibitors Comment Organism Structure
1,3-dimethyl-5-nitro-1H-indazole
-
Homo sapiens
1-(4-chlorobutyl)-5-nitro-1H-indazol-3-ol
-
Homo sapiens
1-benzyl-5-nitro-1H-indazol-3-ol
-
Homo sapiens
1-methyl-5-nitro-1H-indazol-3-ol inhibits MAO-B by 34% at 0.015 mM Homo sapiens
3-(benzyloxy)-5-nitro-1H-indazole
-
Homo sapiens
3-benzyl-5-nitro-1H-indazole
-
Homo sapiens
3-methoxy-1-methyl-5-nitro-1H-indazole inhibits MAO-B by 52% at 0.015 mM Homo sapiens
3-methoxy-5-nitro-1H-indazole
-
Homo sapiens
3-methyl-5-nitro-1H-indazole
-
Homo sapiens
5-nitro-1-(pyridin-2-ylmethyl)-1H-indazol-3-ol
-
Homo sapiens
5-nitroindazole inhibits MAO-B by 98.5% at 0.015 mM Homo sapiens
6-nitroindazole inhibits MAO-B by 89% at 0.015 mM, also inhibits MAO-A Homo sapiens
7-nitroindazole inhibits MAO-B by 35% at 0.015 mM Homo sapiens
Clorgyline
-
Homo sapiens
additional information nitroindazole isomers are good hydroxyl radical scavengers and inhibhit MPTP neurotoxin oxidation by MAO. Compounds 4, 5, 6, 7, 8, 9, 10, and 11 are poor inhibitors Homo sapiens
R-deprenyl
-
Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
Homo sapiens 5739
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine + 2 H2O + 3 O2 Homo sapiens activation of the neurotoxin to neurotoxic pyridinium cations. MPTP easily crosses the blood-brain barrier and is preferentially metabolized by MAO-B present in glial cells to 1-methyl-4-phenyl-2,3-dihydropyridinium. This enzymatic metabolite is subsequently oxidized to 1-methyl-4-phenylpyridinium, which is selectively uptaken by dopaminergic cells, producing inhibition of complex I of mitochondria, energy depletion, oxidative stress and cell death 1-methyl-4-phenyl-2,3-dihydropyridinium + 1-methyl-4-phenylpyridinium + 4 H2O2 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is metabolically oxidized by alpha-carbon oxidation by MAO enzymes to give 1-methyl-4-phenyl-2,3-dihydropyridinium and hydrogen peroxide, which, in a further step, is readily oxidized to 1-methyl-4-phenylpyridinium, that is a directly-acting neurotoxic substance ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Homo sapiens
-
glial cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine + 2 H2O + 3 O2 activation of the neurotoxin to neurotoxic pyridinium cations. MPTP easily crosses the blood-brain barrier and is preferentially metabolized by MAO-B present in glial cells to 1-methyl-4-phenyl-2,3-dihydropyridinium. This enzymatic metabolite is subsequently oxidized to 1-methyl-4-phenylpyridinium, which is selectively uptaken by dopaminergic cells, producing inhibition of complex I of mitochondria, energy depletion, oxidative stress and cell death Homo sapiens 1-methyl-4-phenyl-2,3-dihydropyridinium + 1-methyl-4-phenylpyridinium + 4 H2O2 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is metabolically oxidized by alpha-carbon oxidation by MAO enzymes to give 1-methyl-4-phenyl-2,3-dihydropyridinium and hydrogen peroxide, which, in a further step, is readily oxidized to 1-methyl-4-phenylpyridinium, that is a directly-acting neurotoxic substance ?
2 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine + 2 H2O + 3 O2 activation of the neurotoxin to neurotoxic pyridinium cations Homo sapiens 1-methyl-4-phenyl-2,3-dihydropyridinium + 1-methyl-4-phenylpyridinium + 4 H2O2
-
?
kynuramine + O2
-
Homo sapiens 4-hydroxyquinoline + NH3 + H2O2
-
?
additional information ABTS assay is used to measure total antioxidant activity of nitroindazoles against the radical ABTS*+, overview Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
MAO
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
FAD
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000102
-
5-nitroindazole pH 7.4, 37°C, MAO-B Homo sapiens
0.00067
-
6-nitroindazole pH 7.4, 37°C, MAO-B Homo sapiens
0.0074
-
7-nitroindazole pH 7.4, 37°C, MAO-B Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00099
-
pH 7.4, 37°C, MAO-B Homo sapiens 5-nitroindazole
0.00252
-
pH 7.4, 37°C, MAO-B Homo sapiens 6-nitroindazole
0.0278
-
pH 7.4, 37°C, MAO-B Homo sapiens 7-nitroindazole